NIH Researchers Develop Personalized Breast Cancer Therapy Approach

National Cancer Institute researchers have revealed an experimental form of immunotherapy that uses a patient’s tumor-fighting immune cells to treat those with metastatic breast cancer, advancing personalized medicine.

According to researchers, many individuals with metastatic breast cancer can mount an immune reaction against their tumors, a prerequisite for the immunotherapy that relies on tumor-infiltrating lymphocytes (TILs).

The study results come from an ongoing phase 2 clinical trial designed to see if the immunotherapy approach could lead to tumor regressions in patients with metastatic epithelial cancers. 

In the clinical trial of 42 women with metastatic breast cancer, 67 percent generated an immune reaction against their cancer. The immunotherapy method was used to treat six women, half of whom experienced significant shrinkage of their tumor.

“It’s popular dogma that hormone receptor-positive breast cancers are not capable of provoking an immune response and are not susceptible to immunotherapy,” said Steven A. Rosenberg, MD, PhD, study leader and chief of the surgery branch in NCI’s Center for Cancer Research,  in a press release. “The findings suggest that this form of immunotherapy can be used to treat some people with metastatic breast cancer who have exhausted all other treatment options.”

While immunotherapy helps a person’s own immune system fight cancer, many available immunotherapies have shown limited effectiveness against hormone receptor-positive breast cancers.

However, the immunotherapy approach pursued in the NCI trial relied on TILs, T cells that are found in and around the tumor. TILs can target tumor cells with special proteins, called neoantigens. Neoantigens develop when mutations occur in tumor DNA. Other forms of immunotherapy have been effective in treating cancers that have many mutations, and therefore many neoantigens.

In the trial, the researchers used whole-genome sequencing to detect mutations in tumor samples from 42 women with metastatic breast cancer. The team then isolated TILs from the tumor samples and tested their reactivity against neoantigens produced by different mutations in the tumor.

Researchers found that 28 women had TILs that recognized at least one neoantigen. Almost every neoantigen identified was unique to each patient.

“It’s fascinating that the Achilles’ heel of these cancers can potentially be the very gene mutations that caused the cancer,” said Rosenberg.

According to Rosenberg, with the anticipated opening this year of the NCI’s new building devoted to cell-based therapies, the research team can start treating more individuals with metastatic breast cancer as part of the ongoing clinical trial.

Additionally, Rosenberg noted that the new immunotherapy approach could potentially be used to advance personalized medicine in other types of cancer as well.

“We’re using a patient’s own lymphocytes as a drug to treat the cancer by targeting the unique mutations in that cancer,” he said. “This is a highly personalized treatment.”